Abstract Sub-Saharan Africa, home to more than 1 billion people, is experiencing a stroke epidemic with morbidity and mortality rates that reflect large disparities in clinical outcomes when compared to higher income settings. Limited pharmacological research has been performed to improve post-stroke motor outcomes in the region. Since stroke patients in Sub-Saharan Africa are often younger than in Western countries and have very limited personal wealth, accessible and affordable options that do not depend on the availability of medical experts or expensive treatments would be most impactful. Fluoxetine, a selective serotonin reuptake inhibitor (SSRI) has shown promise in multiple studies of post-stroke recovery. Fluoxetine is widely available throughout the world on Essential Medicines Lists (EMLs) of the World Health Organization for the indication of depression. However, studies of fluoxetine have been performed in relatively small numbers of patients to date, and existing trial findings remain controversial. The use of fluoxetine in Sub-Saharan Africa is untested and not implemented; yet, fluoxetine may be a clinically meaningful and inexpensive option for stroke survivors to improve their motor recovery. This study has two main aims: (1) To build capacity for clinical interventional research on stroke recovery at the Muhimbili National Hospital in Dar es Salaam, Tanzania - a low-income country's main, public, academic teaching hospital - with a focus on setting the stage for a future randomized, placebo-controlled clinical trial; and (2) To determine if fluoxetine 20mg daily, if given within 14 days of acute ischemic stroke onset, is safe and well-tolerated for 90 days post-stroke in 100 new ischemic stroke patients. In order to prepare for the goal of a randomized clinical trial for stroke recovery, significant investments in the training of staff in clinical trial research methods including participant screening, recruitment and enrollment, randomization, use and distribution of placebo, data safety and confidentiality, blinding, study follow up, participant withdrawal and study completion, missing data, and results reporting are required. Each of these tasks will be essential for readying the collaborative Tanzanian-U.S. study team for a randomized, placebo- controlled trial of fluoxetine. Successful completion of Aim 1, demonstrating that capacity will be built for the conduct of stroke clinical trials, will be highly valuable for the Muhimbili National Hospital's stroke unit to broadly prepare for future, interventional stroke research. Successful completion of Aim 2, confirming that fluoxetine is safe and well-tolerated in this population, will provide impetus for a larger, phase III, randomized clinical trial of fluoxetine versus placebo in Sub-Saharan Africa.